Calcium is essential for a number of key functions in the body, both as ionized calcium and a calcium complex. A number of diseases, especially bone-related diseases, are treated/prophylactically treated by intake of a sufficient amount of a calcium-containing compound. Normally, calcium must be orally administered in a relatively high amount, which makes especially dosage forms like e.g. chewable or suckable tablets suitable. However, one of the major problems in this respect is to obtain compositions that have a sufficient customer compliance in order to achieve a correct and efficient treatment. This problem is related to the unpleasant taste and/or mouth feel of calcium-containing compounds, which taste and/or mouth feel is very difficult to mask. Accordingly, the development regarding calcium-containing products for pharmaceutical or nutriceutical use is mainly focused on this taste-masking aspect. To this end, a number of different ways of achieving a suitable taste-masking of a calcium-containing compound have emerged including different manufacturing processes, use of various taste-masking agents and combinations thereof etc.
Another major problem in relation to formulation of calcium-containing solid dosage forms is the size of the dosage form. Normally, a single dose of calcium equals 500 mg (12.5 mmol), which means that, when calcium carbonate is used as calcium source, a single dose contains 1250 mg of calcium carbonate (MW of calcium carbonate is 100). Furthermore, addition of pharmaceutically acceptable excipients is normally required in order to enable tabletting of the calcium-containing compound. This means that the resulting tablet containing a single dose of calcium has a relatively high weight and accordingly, the volume of the tablet is relatively high. It is therefore of utmost importance to seek to minimize the size of the dosage form (e.g. normally in the form of a tablet) as much as possible so that the patient does not find it unpleasant to take the tablet. The size of the tablets is of course of most importance in case of tablets intended for oral administration (to be swallowed). Alternatively, the size of chewing tablets is not that important provided that tablets containing a relevant single dose can be manufactured by means of conventional tabletting equipment. However, in the case dose dispensing is needed the size is critical. Furthermore, chewing tablets should not be too hard to chew, i.e. they should have a crushing strength, which balances the easiness of chewing the tablet and the importance of robustness in order to withstand the normal handling of the tablets. Furthermore, the mouth feel and the taste are of utmost importance in order to ensure patient compliance.
It has been found that the particular method for preparing a particulate material containing the calcium-containing compound influences the taste and mouth-feel of the final product. Thus, it has been found that e.g. a fluid-bed method enables preparation of calcium-containing particulate material that when compressed into tablets have an acceptable taste and mouth-feel in use. In this case, the quality of the calcium-containing compound as well as the method for preparation of a pharmaceutical composition containing the calcium-containing compound are of great importance in order to obtain acceptable taste and mouth feel of a chewable tablet (WO 00/28973). The granulates obtained by this process are manufactured into tablets that have suitable sensory properties, i.e. acceptable mouth feel and taste. However, such tablets must have a suitable small size, a suitable mechanical stability and a suitable mechanical strength to withstand exposure to filling e.g. via a dose-dispensing machine. Furthermore, a fluid-bed process often lead to a very porous granulate which in turn lead to porous tablets, i.e. such tablets may be too large to fit into the cassettes of dose-dispensing machines.
Moreover, the fluid-bed method is not generally applicable to e.g. tablets intended to be sucked or swallowed. The reason is that calcium is dosed in a relatively high amount and in order to include this dosage in a single doses form (tablet), the size of the tablet becomes inconveniently large for a patient to swallow. Accordingly, the fluid-bed process is particular useful in the preparation of chewable tablets, where the size has minor importance.
Calcium-containing tablets suitable for swallowing (i.e. prepared without taking the chalky taste and mouth-feel of the calcium-containing compound into consideration) can be prepared by a process involving e.g. high-shear mixing (WO 96/09036 to Innothera). By using this process a relatively dense granulate is obtained, which in turn leads to tablets of a size that is reduced compared to that obtained when a fluid-bed process is used.
The problem addressed by the present inventors is to provide an alternative method that without preference enables the preparation of a dosage form of a calcium-containing compound in the form of chewable tablets as well as in the form of swallowable tablets. In other words, the known processes are either suitable for use in the preparation of chewable tablets or in the preparation of swallowable tablets. In contrast thereto, a method according to the invention can be used both to prepare chewable tablets and swallowable tablets, respectively.
Such a process has high economical potential, as it will be possible to use the same apparatus in the production of tablets irrespective of whether they are intended for chewing or swallowing. Accordingly, the same production line can easily be shifted from one process to the other and it is not necessary to invest in two separate and different production equipment.
Accordingly, there is a need for developing novel methods that enable preparation of dosage forms like tablets that have a reduced and convenient size for a patient to swallow it and, moreover, also can be used in the preparation of chewable tablets.
Furthermore, due to the difficulty in efficiently masking the chalky taste and the unpleasant mouth feel of calcium, there is a need to develop methods that are suitable for use to obtain an acceptable and good taste.